Showing papers by "Wellcome Trust Centre for Human Genetics published in 1995"
TL;DR: Although it is shown that the insulin gene is expressed biallelically in the adult pancreas, it is presented preliminary evidence that the level of transcription in vivo is correlated with allelic variation within the VNTR.
Abstract: The IDDM2 locus encoding susceptibility to type 1 diabetes was mapped previously to a 41-kb region spanning the insulin gene and a minisatellite or variable number of tandem repeats (VNTR) locus on human chromosome 11p155 By 'cross-match' haplotype analysis and linkage disequilibrium mapping, we have mapped the mutation IDDM2 to within the VNTR itself Other polymorphisms were systematically excluded as primary disease determinants Transmission of IDDM2 may be influenced by parent-of-origin phenomena Although we show that the insulin gene is expressed biallelically in the adult pancreas, we present preliminary evidence that the level of transcription in vivo is correlated with allelic variation within the VNTR Allelic variation at VNTRs may play an important general role in human disease
764 citations
TL;DR: In two large case-control studies of over 2,000 African children, the common African form of G6PD deficiency is associated with a 46á¤-58% reduction in risk of severe malaria for both female heterozygotes and male hemizygotes.
Abstract: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymopathy of humans, affects over 400 million people. The geographical correlation of its distribution with the historical endemicity of malaria suggests that this disorder has risen in frequency through natural selection by malaria. However, attempts to confirm that G6PD deficiency is protective in case-control studies of malaria have yielded conflicting results. Hence, for this X-linked disorder, it is unclear whether both male hemizygotes and female heterozygotes are protected or, as frequently suggested, only females. Furthermore, how much protection may be afforded is unknown. Here we report that, in two large case-control studies of over 2,000 African children, the common African form of G6PD deficiency (G6PD A-) is associated with a 46-58% reduction in risk of severe malaria for both female heterozygotes and male hemizygotes. A mathematical model incorporating the measured selective advantage against malaria suggests that a counterbalancing selective disadvantage, associated with this enzyme deficiency, has retarded its rise in frequency in malaria-endemic regions. Although G6PD deficiency is now regarded as a generally benign disorder, in earlier environmental conditions it could have been significantly disadvantageous.
558 citations
TL;DR: A novel set–recoding scheme is used to recode each person's genotype and ‘fuzzy inheritance’ to infer transmission probabilities and VITESSE enables fast and precise multipoint mappin of disease loci with highly polymorphic markers.
Abstract: As genetic marker maps have improved, multipoint linkage analysis has become a crucial part of all disease mapping studies. Paradoxically, multipoint lod scores become increasingly difficult to compute, particularly as the numbers of markers, marker alleles and untyped people increase. We have solved this problem by using a novel set–recoding scheme to recode each person's genotype and ‘fuzzy inheritance’ to infer transmission probabilities. Our approach is implemented in a memory–efficient computer program, VITESSE, for extremely rapid computation of exact multipoint likelihoods. VITESSE enables fast and precise multipoint mappin of disease loci with highly polymorphic markers.
518 citations
TL;DR: In two unrelated French families linked to CMH4, the authors found a mutation in a splice acceptor site of the MyBP-C gene, which causes the skipping of the associated exon and could produce truncated cardiac My BP-Cs, further supporting the hypothesis that hypertrophic cardiomyopathy results from mutations in genes encoding contractile proteins.
Abstract: Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease characterized by a ventricular hypertrophy predominantly affecting the inter-ventricular septum and associated with a large extent of myocardial and myofibrillar disarray1. It is the most common cause of sudden death in the young. In the four disease loci found, three genes have been identified which code for β-myosin heavy chain, cardiac tro-ponin T and α-tropomyosin2–7. Recently the human cardiac myosin binding protein-C (MyBP-C) gene was mapped to chromosome 11p11.2 (ref. 8), making this gene a good candidate for the fourth locus, CMH4 (ref. 5). Indeed, MyBP-C is a substantial component of the myofibrils that interacts with several proteins of the thick filament of the sarcomere9–13. In two unrelated French families linked to CMH4, we found a mutation in a splice acceptor site of the MyBP-C gene, which causes the skipping of the associated exon and could produce truncated cardiac MyBP-Cs. Mutations in the cardiac MyBP-C gene likely cause chromosome 11-linked hypertrophic cardiomyopathy, further supporting the hypothesis that hypertrophic cardiomyopathy results from mutations in genes encoding contractile proteins.
423 citations
372 citations
TL;DR: Primary etiological components ofIDDM1, the HLA-DQB1 and -DRB1 class II immune response genes, and of IDDM2, the minisatellite repeat sequence in the 5' regulatory region of the insulin gene on chromosome 11p15, have been identified.
Abstract: Whole genome linkage analysis of type 1 diabetes using affected sib pair families and semi-automated genotyping and data capture procedures has shown how type 1 diabetes is inherited. A major proportion of clustering of the disease in families can be accounted for by sharing of alleles at susceptibility loci in the major histocompatibility complex on chromosome 6 (IDDM1) and at a minimum of 11 other loci on nine chromosomes. Primary etiological components of IDDM1, the HLA-DQB1 and -DRB1 class II immune response genes, and of IDDM2, the minisatellite repeat sequence in the 5' regulatory region of the insulin gene on chromosome 11p15, have been identified. Identification of the other loci will involve linkage disequilibrium mapping and sequencing of candidate genes in regions of linkage.
264 citations
TL;DR: Recent developments in several different statistical approaches to linkage analysis of traits involved in susceptibility to common multifactorial diseases are discussed, including affected-sib-pair methods, the affected-pedigree-member method, regressive models and linkage-disequilibrium-based approaches.
252 citations
TL;DR: The utility of polymorphic microsatellites for linkage disequilibrium mapping of genes for complex diseases is demonstrated, with evidence localizes a new diabetes susceptibility gene, IDDM7, to within two centiMorgans of D2S152.
Abstract: The role of human chromosome 2 in type 1 diabetes was evaluated by analysing linkage and linkage disequilibrium at 21 microsatellite marker loci, using 348 affected sibpair families and 107 simplex families. The microsatellite D2S152 was linked to, and associated with, disease in families from three different populations. Our evidence localizes a new diabetes susceptibility gene, IDDM7, to within two centiMorgans of D2S152. This places it in a region of chromosome 2q that shows conserved synteny with the region of mouse chromosome 1 containing the murine type 1 diabetes gene, Idd5. These results demonstrate the utility of polymorphic microsatellites for linkage disequilibrium mapping of genes for complex diseases.
224 citations
TL;DR: These MODY patients exhibit major hyperglycaemia with a severe insulin secretory defect, suggesting that the causal gene is implicated in pancreatic β–cell function.
Abstract: Maturity–onset diabetes of the young (MODY) is a subtype of non–insulin dependent diabetes mellitus, with early age of onset. MODY is genetically heterogeneous, associated with glucokinase mutations and a locus on chromosome 20q; in about 50% of cases, its genetic background is unknown. We have studied 12 families in which MODY is unlinked to either glucokinase or chromosome 20q markers, and find significant evidence for linkage with microsatellite markers on chromosome 12q, most likely within a 7 centimorgan interval bracketed by D12S86 and D12S342. The disease was estimated to be linked to this chromosome region in approximately 50% of families in a heterogeneity analysis. These MODY patients exhibit major hyperglycaemia with a severe insulin secretory defect, suggesting that the causal gene is implicated in pancreatic β–cell function.
210 citations
Journal Article•
TL;DR: An extension of the maximum lod score method of N. Risch is presented, which allows the simultaneous detection and modeling of two unlinked disease loci, and there is seen to be a significant advantage in analyzing more than one locus simultaneously.
Abstract: To investigate the genetic component of multifactorial diseases such as type 1 (insulin-dependent) diabetes mellitus (IDDM), models involving the joint action of several disease loci are important. These models can give increased power to detect an effect and a greater understanding of etiological mechanisms. Here, we present an extension of the maximum lod score method of N. Risch, which allows the simultaneous detection and modeling of two unlinked disease loci. Genetic constraints on the identical-by-descent sharing probabilities, analogous to the {open_quotes}triangle{close_quotes} restrictions in the single-locus method, are derived, and the size and power of the test statistics are investigated. The method is applied to affected-sib-pair data, and the joint effects of IDDM1 (HLA) and IDDM2 (the INS VNTR) and of IDDM1 and IDDM4 (FGF3-linked) are assessed with relation to the development of IDDM. In the presence of genetic heterogeneity, there is seen to be a significant advantage in analyzing more than one locus simultaneously. Analysis of these families indicates that the effects at IDDM1 and IDDM2 are well described by a multiplicative genetic model, while those at IDDM1 and IDDM4 follow a heterogeneity model. 17 refs., 9 tabs.
149 citations
TL;DR: This study shows that the diabetogenic phenotype can be achieved through the actions of variable combinations of MHC-unlinked genes and a diabetogenesis MHC haplotype through outcrossing NOD mice to other inbred strains congenic for the NOD M HC haplotype.
Abstract: Chromosome locations of non–major histocompatibility complex (MHC) genes contributing to insulin-dependent diabetes mellitus (IDDM) in mice have been determined by outcrossing NOD mice to other inbred strains congenic for the NOD MHC haplotype ( H2g7 ). At least nine non-MHC IDDM susceptibility genes ( Idd ) were previously identified at first backcross (BC1) after outcross of NOD to C57BL/10. H2g7 congenic mice (B10. H2g7 ). We investigated whether the same set of Idd loci segregated with IDDM susceptibility after outcross of NOD to NON. H2g7 congenic mice. Since the outcrosses to NON. H2g7 and B10. H2g7 were performed in the same vivarium, direct comparisons were made of the chromosomal locations and relative strengths of Idd alleles in diabetic progeny from the two different outcrosses. In comparison with the NOD × B10. H2g7 outcross, the NOD × NON. H2g7 outcross produced significantly higher IDDM frequencies in F1, F2, and BC1 generations. The high F2 diabetes frequency allowed evaluation of the effects of homozygous expression of both the susceptibility and the resistance allele at Idd loci. This analysis demonstrated that no single non-MHC Idd locus was essential for the onset of diabetes in this cross. After outcross to NON. H2g7 , Idd4 (chromosome [Chr] 11), Idd5 (Chr 1), and Idd8 (Chr 14) did not segregate with IddM in either the BC1 or the F2 generation. Diabetogenic NOD-derived alleles at Idd2 (Chr 9), Idd3 (Chr 3), and Idd10 (Chr 3) were segregating in the BC1. An NON-derived allele contributing to susceptibility on Chr 7 ( Idd7 ) was also detected. Dominant traits, detectable only in the F2 cross, were encoded by Chr 4 ( Idd9 ) and two newly mapped loci on Chr 13 ( Idd14 ) and 5 ( Idd15 ). A third dominant trait was encoded by Chr 6 (possibly Idd6 ), but here, in contrast to Idd9 , Idd14 , and Idd15 , the NON allele was diabetogenic. Stepwise logistic regression analysis of the BC1 and F2 data confirmed that the ability to identify certainty of the non-MHC Idd loci was contingent on the extent of homozygosity for NOD background genes. This study shows that the diabetogenic phenotype can be achieved through the actions of variable combinations of MHC-unlinked genes and a diabetogenic MHC haplotype.
TL;DR: Three major resistance loci are mapped to mouse chromosomes 5 and 7 and the results indicate that benign and malignant tumours are largely under independent genetic control.
Abstract: Genetic susceptibility to chemically induced skin cancer in mice is controlled by multiple unlinked genetic loci. Mus spretus mice have dominant resistance genes which confer resistance to interspecific F1 hybrids with susceptible Mus musculus strains. We have mapped three major resistance loci using a combination of Mapmaker/QTL analysis and multiple regression analysis to mouse chromosomes 5 and 7. At least two independent loci on chromosome 7 exert their effects primarily during benign tumour development and have very little influence on tumour progression. On the other hand, probably a single locus on chromosome 5 affects both early and late stages of malignancy. The results indicate that benign and malignant tumours are largely under independent genetic control.
Journal Article•
TL;DR: It is concluded that two QTLs jointly influence serum ACE levels in this population and the identification of the molecular mechanisms underlying bothQTLs is necessary in order to interpret the role of ACE in cardiovascular disease.
Abstract: Human serum angiotensin I-converting enzyme (ACE) levels vary substantially between individuals and are highly heritable. Segregation analysis in European families has shown that more than half of the total variability in ACE levels is influenced by quantitative-trait loci (QTL). One of these QTLs is located within or close to the ACE locus itself. Combined segregation/linkage analysis in a series of African Caribbean families from Jamaica shows that the ACE insertion-deletion polymorphism is in moderate linkage disequilibrium with an ACE-linked QTL. Linkage analysis with a highly informative polymorphism at the neighboring growth-hormone gene (GH) shows surprisingly little support for linkage (LOD score [Z] = 0.12). An extended analysis with a two-QTL model, where an ACE-linked QTL interacts additively with an unlinked QTL, significantly improves both the fit of the model (P = .002) and the support for linkage between the ACe-linked QTL interacts additively with an unlinked QTL, significantly improves both the fit of the model (P = .002) and the support for linkage between the ACe-linked QTL and GH polymorphism (Z = 5.0). We conclude that two QTLs jointly influence serum ACE levels in this population. One QTL is located within or close to the ACE locus and explains 27% of the total variability; the second QTL is unlinked to the ACE locus and explains 52% of the variability. The identification of the molecular mechanisms underlying both QTLs is necessary in order to interpret the role of ACE in cardiovascular disease.
TL;DR: This work has shown that the major disease locus, IDDM1 in the major histocompatibility complex on chromosome 6p21, accounts for about 35% of the observed familial clustering and its contribution to disease susceptibility is likely to involve polymorphic residues of class II molecules in T-cell-mediated autoimmunity.
TL;DR: It is demonstrated that many of the polymorphisms found to be associated with IDDM in other Caucasoid populations do not show any association in this Finnish population and it has been demonstrated that the –23 Hph I polymorphism cannot explain the association.
Abstract: The gene region on chromosome 11p15.5 known to be involved in insulin-dependent diabetes mellitus (IDDM) susceptibility was recently mapped to a 4.1-kilobase region including the insulin gene. The region contains 10 candidate polymorphisms that are in strong linkage disequilibrium. By genotyping 7 of these 10 polymorphisms and the tyrosine hydroxylase microsatellite in Finnish Caucasoid IDDM patients and control subjects, we demonstrate that many of the polymorphisms found to be associated with IDDM in other Caucasoid populations do not show any association in this Finnish population. Of the polymorphisms typed, only those at -23 Hph I and the variable number of tandem repeats (VNTR) sites confer significant relative risk. Furthermore, we have demonstrated that the -23 Hph I polymorphism cannot explain the association. Comparison of the genotypic patterns observed here and previously suggests that the VNTR is the most likely candidate for IDDM2. The VNTR is located adjacent to defined regulatory DNA sequences affecting insulin gene expression, which suggests a possible effect on expression of insulin or one of the neighboring genes, tyrosine hydroxylase or insulin-like growth factor 2.
TL;DR: A linkage of the cystinosis gene to markers on the short arm of chromosome 17 (Zmax=10.89, θ=0.03) for marker D17S1584 was reported in this paper.
Abstract: Nephropathic cystinosis (MIM 21980) is an autosomal recessive disorder due to defective transport of the amino acid cystine out of lysosomes1. Cystine storage leads to acidosis, dehydration, rickets and growth retardation in the first year of life, followed by renal glomerular failure at approximately ten years of age2. Renal transplantation is highly successful, but cystine continues to accumulate in other tissues, resulting in complications such as corneal ulcerations and retinal blindness, a distal vacuolar myopathy, delayed puberty, swallowing difficulties, pancreatic deficiency and central nervous system involvement2,3. Treatment with the cystine-depleting agent, cysteamine (CystagonR), or phosphocysteamine, has proven successful in retarding glomerular deterioration and enhancing growth4,5. Although cystinosis represents the prototypic disorder of lysosomal membrane transport, neither the cystinosis gene nor the lysosomal cystine carrier has been isolated. We now report linkage of the cystinosis gene to markers on the short arm of chromosome 17 (Zmax=10.89, θ=0.03) for marker D17S1584. Multipoint analysis and haplotypes in recombinant families suggest that the gene is located between markers D17S1583 and D17S796.
TL;DR: Construction of congenic mouse strains, and the exploitation of linkage disequilibrium between very closely linked markers and disease-predisposing loci, is enabling fine mapping of these loci in humans.
TL;DR: This work has undertaken to saturate the A-T region with highly polymorphic microsatellite markers, and has identified seven new polymorphic CA-repeats in this region, and mapped to it five new markers generated by Genethon and the Cooperative Human Linkage Center.
Abstract: The locus of the autosomal recessive disorder ataxia-telangiectasia (A-T) has been assigned by linkage analysis with biallelic markers to a 4-Mb interval on chromosome 11q22-23, between GRIA4 and D11S1897. We have undertaken to saturate the A-T region with highly polymorphic microsatellite markers. To this end, we have identified seven new polymorphic CA-repeats in this region, and have mapped to it five new markers generated by Genethon and the Cooperative Human Linkage Center. These markers are in addition to 12 others that we have previously mapped or generated at the A-T locus. All 24 markers have been integrated into a high-density microsatellite map spanning some 6 Mb DNA. This map, which contains the A-T locus and flanking sequences, allows the construction of extensive, highly informative haplotypes.
TL;DR: Genotype analysis with COL7A1 polymorphic markers, or direct COL 7A1 mutation detection in families at risk for the disease, represent early and rapid diagnostic alternatives to second-trimester evaluation of fetal skin samples, and thus offer a major advance in prenatal diagnosis of this life-threatening form of epidermolysis bullosa.
TL;DR: Using an intragenic simple sequence repeat polymorphism, linkage of the COL5A1 gene, which encodes the alpha 1(V) chain of type V collagen, to EDS II is reported.
Abstract: Ehlers-Danlos syndrome (EDS) is a group of heritable disorders of connective tissue with skin, ligaments and blood vessels being the main sites affected. The commonest variant (EDS II) exhibits an autosomal dominant mode of inheritance and is characterized by joint hypermobility, cigarette paper scars, lax skin and excessive bruising. As yet no gene has been linked to EDS II, nor has linkage been established to a specific region of the genome. However, several candidate genes encoding proteins of the extracellular matrix have been excluded. Using an intragenic simple sequence repeat polymorphism, we report linkage of the COL5A1 gene, which encodes the alpha 1(V) chain of type V collagen, to EDS II. A maximum LOD score (Zmax) for linkage of 8.3 at theta = 0.00 was generated for a single large pedigree.
TL;DR: Development of novel congenic mouse strains has allowed us to better define the location of the diabetogenic locus, Idd3, on Chromosome (Chr) 3.
Abstract: Development of novel congenic mouse strains has allowed us to better define the location of the diabetogenic locus, Idd3, on Chromosome (Chr) 3. Congenic strains were identified by use of published and newly developed microsatellite markers, their genomes fingerprinted by a rapid, fluorescence-based approach, and their susceptibility to type 1 diabetes evaluated. The maximum interval containing Idd3 is now approximately 4 cM.
TL;DR: Examination of patients from three geographically distinct regions in the UK found the GGT40 to AGT40 (Ser) mutation to be present in 15/691 of patients with type 2 (non-insulin dependent) diabetes and 1/425 of geographically matched controls and replicated association of the GCG-R mutation with classical type 2 diabetes.
Abstract: Recent evidence suggests that a mutation of the glucagon receptor (GCG-R) gene is involved in the development of type 2 diabetes in French patients. We have examined patients from three geographically distinct regions in the UK and found the GGT40 (Gly) to AGT40 (Ser) mutation to be present in 15/691 (2.2%) of patients with type 2 (non-insulin dependent) diabetes and 1/425 (0.2%) of geographically matched controls and have therefore replicated association of the GCG-R mutation with classical type 2 diabetes (Fisher's exact test p = 0.008). An increased frequency of the mutation of the GCG-R gene was also found in probands of type 1 (insulin dependent) diabetic multiplex (affected sib pair) families, (10/404, 2.5%). However, a lack of preferential transmission from parents heterozygous for the mutation, to affected type 1 diabetic sibs may suggest population stratification. This in turn cannot be excluded as an alternative explanation for the difference in frequency of the GCG-R gene mutation between subjects with type 2 diabetes and normal controls.
TL;DR: Results constitute the first steps in constructing a physical gene map for Z. biebersteiniana and may facilitate future studies of the organization and reorganization of grass genomes, including research into the spatial arrangement of the genome inZingeria nuclei and much wider comparisons of synteny and genome evolution in grasses.
Abstract: The grassZingeria biebersteiniana is one of five angiosperms known with 2n=2x=4. Its chromosomes were studied using fluorochrome banding and fluorescencein situ hybridization (FISH). The large pericentromeric region fluoresced much more brightly on chromosome 2 than on chromosome 1, using two different fluorochrome banding methods. These offer rapid and reliable means for identifying chromosomes and work throughout mitosis. FISH located the major site of 18S–26S rDNA sequences at the secondary constriction, which is proximal to two minor sites, all on the short arm of chromosome 1. Two 5S sites were also detected, the most distinct on the short arm of chromosome 2 and the other apparently co-localized with part of the major 18S–26S rDNA cluster on chromosome 1. These results constitute the first steps in constructing a physical gene map forZ. biebersteiniana. Such information may facilitate future studies of the organization and reorganization of grass genomes, including research into the spatial arrangement of the genome inZingeria nuclei and much wider comparisons of synteny and genome evolution in grasses.
TL;DR: The Maximum Lod Score method for affected relative‐pair analysis is extended to be applicable to X‐chromosomal data, and genetic restrictions on the haplotype‐sharing probabilities analogous to the ‘possible triangle’ restrictions described by Holmans for the autosomal case are derived.
Abstract: SUMMARY
The Maximum Lod Score method for affected relative-pair analysis, introduced by Risch, is a powerful method for detecting linkage between an autosomal marker locus and disease. In order to use the method to detect linkage to markers on the X-chromosome, some modification is necessary. Here we extend the method to be applicable to X-chromosomal data, and derive genetic restrictions on the haplotype-sharing probabilities analogous to the ‘possible triangle’ restrictions described by Holmans for the autosomal case. Size criteria are derived using asymptotic theory and simulation, and the power is calculated for a number of possible underlying models. The method is applied to data from 284 type 1 diabetic families and evidence is found for the presence of one or more diabetogenic loci on the X-chromosome.
TL;DR: The allelic association between P225S and xIRP alleles suggests a common ancestral chromosome bearing the P 225S variant and an RP3 mutation at a neighbouring locus.
Abstract: A novel gene encoding a 2.2 kilobase transcript has been isolated from the Xp21.1 region of the human X chromosome by exon amplification. The gene, called EXT1, spans 80 kilobases and contains 12 exons, at least two of which are alternatively spliced and have predicted products of 464 and 471 amino acids respectively. Conceptual translation of the open reading frames shows one product with a 30 amino acid signal peptide, which is absent from the alternative transcript, followed by three complement control protein domains, a hydrophobic region with a possible role in membrane anchorage and short 17 amino acid putative cytoplasmic carboxyl terminus. An alternative first exon contains a 39 amino acid open reading frame which is rich in serine and threonine residues and contains a potential chondroitin/dermatan sulphate attachment site. Northern analysis showed ETX1 expression within the retina and heart with lower levels in several other tissues. Since ETX1 lies within the region thought to contain the x-linked retinitis pigmentosa (xIRP) gene, RP3, it was screened for mutation within a set of 45 xIRP patients using single strand conformation analysis and/or chemical cleavage of mismatch using reverse transcription/polymerase chain reaction amplification of polyA+RNA from blood cells. Three low frequently variants (17-23Ldel, P225S, S413F) were found in both patients and controls; one of which (P225S) was found in four of 45 unrelated patient chromosomes and one of 178 control chromosomes (p <0.001). The allelic association between P225S and xIRP alleles suggests a common ancestral chromosome bearing the P225S variant and an RP3 mutation at a neighbouring locus.
TL;DR: The physical localization of 36 additional polymorphic markers by polymerase chain reaction analysis is reported, which will facilitate the construction of a YAC contig of the q13-q21 region of the human X chromosome.
TL;DR: Three yeast artificial chromosome contigs spanning approximately 7 megabases of the Xq13.3-q21.31 region are generated and a novel deletion associated with choroideremia and mental retardation was identified and mapped in detail.
Abstract: Microscopically detectable deletions and X;autosome translocations have previously facilitated the construction of a high-resolution interval map of the Xq21 region. Here, we have generated three yeast artificial chromosome contigs spanning approximately 7 megabases of the Xq13.3-q21.31 region. In addition, a novel deletion associated with choroideremia and mental retardation was identified and mapped in detail. The proximal deletion endpoint was positioned between the loci DXS995 and DXS232, which enabled us to confirm the critical region for a locus involved in mental retardation. The distal deletion endpoint is situated in the Xq21.33 band, which allowed us to refine the order of several markers in this region.
TL;DR: 11. Taniguchi, T., Minami Y.S., McBride, O.W., Leonard, W.D., Greenberg, P.H., Lord, J.D. (1994).
Abstract: 11. Taniguchi, T., Minami Y. (1993). Cell 73, 5-8. 12. Bazan, J.F. (1990). Proc. Natl. Acad. Sci. USA 87, 6934. 13. Nakamura, Y., Russell, S.M., Mess, S.A., Friedman, M., Erdos, M, Francois, C., Jacques, Y., Adelstein, S., Leonard, W.J. (1994). Nature 369, 330-333. 14. Nelson, B.H., Lord, J.D., Greenberg, P.D. (1994). Nature 369, 333336. 15. Noguchi, M., Yi, H., Rosenblatt, H.M., Filipovich, A.H., Adelstein, S., Modi, W.S., McBride, O.W., Leonard, W.J. (1993). Cell 73, 147-157. 16. Webb, G.C., Campbell, H.D., Lee, J.S., Young, I.G. (1990). Cytogenet. Cell Genet. 54, 164-168. 17. Campbell, H.D., Webb, G.C., Kono, T., Taniguchi, T., Ford, J.H., Young, I.G. (1992). Genomics 12, 179-180. 18. Kawamura, H., Sharrow, S.O., Ailing, D.W., Stephany, D., YorkJolley, J., Berzofsky, J.A. (1986). J. Exp. Med. 163, 1376-1390. 19. Malek, T.R., Vincek, V., Gatalica, B., Bucan, M. (1993). Immunogenetics 38, 154-156.
TL;DR: Two new polymorphic (CA), dinucleotide microsatellite repeats in the rat DMD gene are isolated, one near exon 29 towards the 5' end of the gene, the other in the 3' untranslated region.
Abstract: The human dystrophin (DMD) gene contains at least 79 exons, five different promoters, and spans approximately 2.5 Mb and 12 cM of the X Chromosome (Chr; Ahn and Kunkel 1993; Abbs et al. 1990).
We have isolated two new polymorphic (CA), dinucleotide microsatellite repeats in the rat DMD gene, one near exon 29 towards the 5' end of the gene, the other in the 3' untranslated region. The Y (CA)n microsatellite is conserved between species, present at the same location in the rat, mouse, and human genes (Maichele and Chamberlain 1992). Both the microsatellites are polymorphic between
different rat strains, making them useful markers for mapping in rat genetic crosses.